NCT07377591
Recruiting
Phase 1
A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of HDM2006 Monotherapy in Patients With Advanced Solid Tumors
Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.1 site in 1 country48 target enrollmentStarted: December 31, 2024Last updated:
InterventionsHDM2006
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Incidence of dose limiting toxicity (DLT) events (for dose escalation phase)
Overview
Brief Summary
This is a first-in-human (FIH) study to evaluate the safety and preliminary efficacy of experimental drug HDM2006 in patients with advanced solid tumors.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1\. The subjects understand and voluntarily (or legally authorized guardian) sign a written informed consent form (ICF) approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC).
- •2\. Males or females aged ≥ 18 years old.
- •In the dose escalation phase, subjects must have histologically or cytologically confirmed advanced or metastatic solid tumors, who have experienced adequate standard treatment failure, intolerance to standard treatment, or lack of effective standard treatment.
- •4\. In the dose expansion phase, subjects must have histologically or cytologically confirmed advanced or metastatic specific types of tumors, who have experienced adequate standard treatment failure, intolerance to standard treatment, or lack of effective standard treatment. These include, but are not limited to, head and neck squamous cell carcinoma, renal cell carcinoma, cervix carcinoma, and other advanced solid tumors, as well as tumor types that showed efficacy signals (CR/PR) in the dose escalation phase.
- •5\. In the dose expansion phase, subjects are able to provide fresh or archival (within one year) tumor tissues at the time of screening and are willing to provide tumor tissue biopsy after administration of HDM2006 for baseline and post-treatment biomarker analysis.
- •6\. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 or 1 .
- •7\. Expected survival time \> 3 months.
- •According to the Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), subjects in phase 1a must have at least one evaluable lesion, and subjects in phase 1b must have at least one measurable lesion (a lesion located in areas previously treated with radiotherapy will not be considered a measurable lesion unless there is sufficient evidence to show clear imaging progression of the lesion after radiotherapy; biopsy lesions should be excluded for measurable lesions in subjects in phase 1b).
- •9\. The subject has good organ function as indicated by laboratory results at screening (no cytokine or other corrective medications are allowed within 14 days prior to laboratory tests at screening):Hematology: a) absolute neutrophil count ≥ 1.5 × 10\^9/L (1500/mm3); b) platelet count ≥ 100 × 10\^9/L (no platelet transfusion within 14 days prior to the investigation); c) hemoglobin ≥ 9.0 g/dL (no red blood cell transfusion within 30 days prior to the investigation); Liver: a) serum total bilirubin ≤ 1.5 × ULN; b) AST and ALT ≤ 3 × ULN (≤ 5 × ULN for subjects with tumor liver metastasis); c) serum albumin ≥ 30 g/L (no albumin transfusion within 21 days prior to investigation); Kidney: blood creatinine ≤ 1.5 × ULN; or creatinine clearance (CrCl) ≥ 50 mL/min (calculated by Cockcroft-Gault formula, see Appendix 4); Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (unless the subject is receiving anticoagulant therapy, and the coagulation parameters \[PT/INR and APTT\] are within the expected range for anticoagulant therapy at screening).
- •10\. Women of childbearing potential (WOCBP) must be willing to use 2 adequate methods of contraception or barrier contraception plus hormonal contraception from the time of signing ICF until 6 months after the last dose of study treatment to prevent pregnancy or abstain from heterosexual activity throughout the study; male subjects must agree to take adequate contraceptive measures from the first dose of study treatment until 6 months after the last dose of study treatment .
Exclusion Criteria
- •1\. Subjects who are concurrently participating in another clinical study, unless it is an observational (non-interventional) clinical study or they are in the survival follow-up period of an interventional study.
- •2\. Subjects with the following treatments:
- •Subjects who have received major surgery within 4 weeks prior to the first dose, excluding minor surgery, such as appendicitis surgery, tissue acquisition for tumor biopsy, etc.;
- •Subjects who have received bone marrow (equivalent to pelvic bone marrow area) or extensive radiotherapy within 28 days prior to the first dose; subjects who have received local radiotherapy (e.g., thoracic and rib radiotherapy) within 7 days prior to the first dose of the study drug;
- •Subjects who have previously received HPK1 inhibitor treatment.
- •Subjects who have history of active malignancies within the past 2 years, with the exception of tumors in this study and cured local tumors, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, cervix carcinoma in situ, breast cancer in situ, etc.
- •4\. Subjects who have not recovered (i.e., recover to ≤ Grade 1 or baseline) from related AEs (such as alopecia, ≤ Grade 2 sensory neuropathy, or other ≤ Grade 2 AEs that do not pose a safety risk as judged by the investigator) resulting from previous treatments or other anti-tumor therapies.
- •5\. Subjects with unstable brain metastasis: subjects with central nervous system complications requiring emergency neurosurgery (e.g., surgery) (excluding those who have completed surgery for more than 7 days and whose complications have resulted in ≤ Grade 1 side effects);
- •Subjects with epilepsy requiring treatment; subjects with a history of psychotropic drug abuse and unable to abstain or have mental disorders (those who have abstained must meet an observation period without withdrawal reactions for at least 2 weeks).
- •7\. Subjects with any of the following cardiovascular diseases/symptoms/signs:
Arms & Interventions
HDM2006
Experimental
In dose escalation phase, participants will be administered escalating doses of HDM2006 at 50 mg QD, ~1000 mg QD, Oral administration within half an hour after a meal. In dose expansion phase, participants will be administered to recommended dose for expansion (RDE) of HDM2006, Oral administration within half an hour after a meal.
Intervention: HDM2006 (Drug)
Outcomes
Primary Outcomes
Incidence of dose limiting toxicity (DLT) events (for dose escalation phase)
Time Frame: up to 21 days following first dose
DLT will be determined by definition during the DLT observation period.
Incidence and severity of adverse events(for dose escalation phase)
Time Frame: Until 30 days after the last dose or initiation of a new antineoplastic therapy, whichever occurs first
The safety profile of HDM2006 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Change from baseline in HPK1 expression in tumor tissues (dose expansion)
Time Frame: through study completion, an average of 1 year
HPK1 expression levels will be measured using Flow Cytometry. The unit of measure is percentage of positive cells.
Changes from baseline in pSLP-76 expression in tumor tissue (dose expansion)
Time Frame: From baseline through study completion, an average of 1 year
pSLP-76 expression levels will be measured using Flow Cytometry. The unit of measure is percentage of positive cells.
Recommended Phase 2 Dose (RP2D) (for dose expansion phase)
Time Frame: through study completion, an average of 1 year
The specific dose level of HDM2006 identified for use in the Phase 2 expansion phase
Secondary Outcomes
- Plasma concentration of HDM2006(up to7 days following last dose)
- Objective Response Rate (ORR)(for dose escalation phase)(through study completion, an average of 1 year)
- Time to Response (TTR)(From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Progression free survival (PFS)(From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Duration of Response (DOR)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to100 months)
- Overall survival (OS)(From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
Investigators
Study Sites (1)
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